Alpha-1 Antitrypsin Deficiency (Alpha-1) is one Healthcare Provider’s Guide
of the most common serious hereditary A Healthcare Provider’s Guide to Alpha-1 Antitrypsin Deficiency
is a response by the Alpha-1 Foundation to the need for
disorders. Alpha-1 has been identified in providing up-to-date information about screening, diagnosis and
virtually all populations but is most common in treatment of this disorder. Materials in this physician information
individuals of Northern European (Scandinavian packet are designed to educate physicians, their staff members,
and patients about AAT Deficiency and available resources. An
and British) and Iberian (Spanish and Education Materials Working Group assists the Foundation’s
Portuguese) descent. Among patients with Medical And Scientific Advisory Committee (MASAC) in
identifying, producing and reviewing educational and training
Chronic Obstructive Pulmonary Disease
materials. The Working Group is comprised of a wide range of
(COPD), 1-3% are predicted to have AAT professionals, such as bioethicists, physicians and nurses, and
Deficiency. It can also cause life threatening educators who contribute their expertise. AAT deficient
individuals are also members of the Working Group to ensure
liver damage in adults and children and liver
that the patient point of view is incorporated. Acknowledgment is
cancer in adults. Despite its prevalence, made to all of these individuals and the many other people who
patients and healthcare providers have been have provided insightful and helpful editorial comments. Also
available are three additional educational materials for your
poorly informed about the disorder. For this and
patients, available in English and Spanish:
other reasons, the overwhelming majority of What is Alpha-1 Antitrypsin Deficiency?
individuals with AAT Deficiency have not been Should I Be Tested?
detected. Of the 100,000 individuals in the A Guide for the Recently Diagnosed Patient.
United States estimated to have AAT Deficiency, A Guide for Carriers of Alpha-1.
less than 10% have been diagnosed, leaving
more than 90,000 affected individuals
undetected. For additional information
on the Alpha-1 Foundation contact:
The discovery of Alpha-1 Antitrypsin (AAT) Deficiency by Laurell
2937 SW 27th Avenue, Suite 302
and Erickson in 1963 provided a foundation for current thinking
Miami, Florida 33133
about the pathogenesis of pulmonary emphysema. Although AAT
Telephone: (305) 567-9888
Deficiency has become one of the best-understood genetic
Fax: (305) 567-1317
disorders at a molecular and cellular level, many questions about
Toll Free: (877) 2-CURE-A1 (228-7321)
the clinical disorder remain unanswered.
Web Site: www.alphaone.org
The Alpha-1 Foundation, the National Institutes of Health (NIH) E-mail: email@example.com
and pulmonary and liver disease experts are working aggressively
to develop patient management and clinical treatment guidelines
for working with patients affected by AAT Deficiency.
Version 1.6 ® 2003 Alpha-1 Foundation, 11/03
What Is Alpha-1 Antitrypsin? What is Alpha-1 Antitrypsin Deficiency?
Alpha-1 Antitrypsin (AAT) is a protein that circulates in the blood. Alpha-1 Antitrypsin (AAT) Deficiency is a genetic disorder
Some scientists also call it “alpha1-proteinase inhibitor.” The liver characterized by the production of an abnormal AAT protein.
makes most of the circulating AAT in the blood. The liver cells cannot secrete the abnormal AAT protein, which
AAT protects the tissues of the body from being damaged by accumulates within the cells and results in marked reductions of
proteolytic enzymes (substances that break circulating AAT levels. Although the mechanisms are not
down proteins), especially neutrophil elastase completely known, it is believed that the retained abnormal AAT
(substance released by white blood cells in protein over time leads to liver injury in some affected persons.
response to lung irritation or infection). In the lungs, low-levels of AAT allow for the destructive effects of
neutrophil elastase to go unchecked, which results in damage to
Structural representation the delicate gas exchange region of the lungs (alveoli),
of Alpha-1 Antitrypsin. eventually leading to emphysema as young as 30 years of age.
Thus, persons with AAT Deficiency are at high risk of developing
life-threatening liver and lung disease.
Epidemiology of AAT Deficiency
AAT Deficiency is the most prevalent potentially fatal genetic diagnosed in adults in all decades. Finally, some persons with
disorder of adult Caucasians in the U.S., which occurs equally in AAT Deficiency can live completely normal life spans without
men and women. The incidence of AAT Deficiency in the general significant symptoms, especially if they are non-smokers.
Caucasian population is estimated between 1/2500 and 1/3000 in Liver disease related to AAT Deficiency can manifest at any age. In
the U.S.; as a comparison, Cystic Fibrosis has an incidence in infancy, the liver disease commonly takes the form of “prolonged
whites of 1/2500 at birth. obstructive jaundice.” AAT Deficiency should be suspected in
Untargeted screening studies of large populations have revealed older children, adolescents and adults with elevated liver enzymes,
a variable prevalence of AAT Deficiency, depending upon where prolonged clotting tests, enlarged liver and/or spleen, portal
the studies have been done. In addition, there have been several hypertension, esophageal varices, ascites, chronic active hepatitis
reports of screening studies in smaller populations of targeted or “cryptogenic” cirrhosis. AAT Deficiency is the leading genetic
individuals. These individuals have included adults with cause of liver disease in infants and children and is the second
emphysema, chronic bronchitis, COPD, bronchiectasis, and most common indication for liver transplantation in this group in the
asthma, as well as children with chronic liver disease. These U.S. The risk of hepatocellular carcinoma is increased in persons
targeted populations were identified based on the increased with AAT Deficiency. However, the rate of liver disease progression
prevalence of these conditions among persons with AAT in affected individuals, even those with severe disease, may be
Deficiency. However, more studies are needed to prove that AAT relatively slow, so that AAT deficient individuals may lead a
Deficiency is more prevalent in these targeted disease groups. relatively normal life. Recent evidence suggests that there is some
AAT Deficiency can appear as a chronic lung disease (i.e., increased risk of liver and lung disease in persons with who are
emphysema, chronic bronchitis, COPD, bronchiectasis, and Z-allele heterozygotes (Pi MZ), although these issues are still under
asthma) in adults as early as the third decade of life, especially investigation. Liver disease has not been identified in persons with
in smokers. Nevertheless, symptomatic AAT Deficiency can be the rare Pi Null/Null phenotype, who do not produce any AAT protein.
Genetics of AAT Deficiency
The accumulated knowledge about AAT Deficiency is the result The most prevalent type of deficient allele associated with AAT
of many studies conducted worldwide. The two most important Deficiency is the Z allele. More than 95% of individuals with AAT
genetic aspects of AAT Deficiency are: (1) the understanding Deficiency have phenotype Pi Z (that is, express only the Z variant
that there are many alleles for the protein and (2) that the clinical in the plasma); there are at least 20 other rare allele variants that
manifestations (lung and liver disease) result from specific comprise the rest of the 5% of the AAT deficient population.
combinations of alleles. The Z variant is subtly abnormal as an inhibitor of neutrophil
A pair of alleles at the proteinase inhibitor (Pi) locus controls the elastase. However, the most striking abnormality in affected
synthesis of AAT. The genes are inherited as co-dominant alleles individuals is that circulating levels of the protein are only 10-
(products from both genes can be found in the circulation). AAT 15% of normal. When livers of these individuals are examined,
in the serum can be characterized by phenotyping (identifying the hepatocytes contain an abnormal accumulation of AAT.
the expressed AAT proteins in the body), which is accomplished The Pi Z type of AAT cannot be released effectively from liver
by isoelectric focusing. There are more than 90 different allelic cells. As a result, the levels in the blood are decreased and the
variants of AAT but many of these are quite rare. retained AAT may cause injury to the liver.
A Pi allele associated with mild AAT deficiency is the S allele,
Phenotype What Does It Mean? producing the S variant protein. The S mutation is not associated
Pi Z (ZZ) (Homozygote) Patient HAS with intracellular accumulation of the protein, and the S protein
Alpha-1 Antitrypsin Deficiency inhibits elastase nearly normally. The S allele is slightly more
prevalent than the Z allele. Individuals with Pi S phenotype do
Pi MZ (Heterozygote) Patient is a CARRIER of
not appear to be at an increased risk for lung or liver disease
Alpha-1 Antitrypsin Deficiency
(Pi S individuals who are heterozygous with the Z allele are
and can pass these genes on
discussed further below).
to their children
Another allelic variation is represented by the null alleles. The
Pi M (MM) Patient does NOT have
Alpha-1 Antitrypsin Deficiency null alleles express no AAT in the blood. Note that in Pi Z
individuals, isoelectric focusing reveals only an abnormally
Please note that phenotyping for AAT Deficiency is very migrating Pi Z type AAT. These individuals may be either Pi ZZ
complicated. When we refer to the “phenotype” in this disorder, homozygotes or Pi Z/null heterozygotes, since no AAT
we are referring to the protein TYPES. The most common variants attributable to the null genes can be found in the circulation.
of AAT Deficiency are discussed in detail below; there are also There has been no evidence of liver disease in the Pi Null/Null
many other possibilities. population. Also, in cases of Pi M phenotypes associated with
For this reason it is easier to group the variants into categories: low levels of AAT, there may be a possibility that a null allele
(1) normal variants of AAT (those that produce and distribute AAT might be present. Family studies of the pattern of inheritance
normally in the serum); and (2) deficient variants (those that and further documentation are necessary to distinguish between
produce reduced or no AAT levels in the serum) and which lead to the possibilities.
an increased risk of AAT Deficiency-related lung and liver disease.
Common Alleles: Pi MS individuals have one normal allele and one S allele. They
The family of the normal AAT alleles is referred to as M. The M alleles have nearly normal, and occasionally normal, levels of AAT. They
are the most common types of AAT gene and result in normal do not appear to be at an increased risk for lung or liver disease.
amounts and normal functionality of AAT in the blood. About 95% of Pi MZ individuals have one normal allele and one Z variant (the
the population of the United States has only M alleles. There are other classical deficiency variant). They usually have decreased levels
normal alleles, and at least four identified variants of the M allele. of AAT in their circulation; however, their levels can fall within the
normal range. Although this issue remains under investigation, For example:
recent studies suggest that Pi MZ heterozygotes may have an AAT Deficiency is a genetic disorder. Look at the figure below to
increased risk for developing lung or liver disease, At present, it see the possible outcomes for children if both parents are carriers
seems prudent to reassure Pi MZ heterozygotes regarding their of an abnormal AAT gene.
potential risk for developing lung or liver disease, and to counsel
them about the risk of genetic transmission of the deficient allele. FATHER MOTHER
You should recommend that the patient avoid tobacco smoking.
Pi SZ individuals have one allele for the S variant and one for the Z Z
deficient Z variant. Pi SZ heterozygotes are more common than
those with Pi ZZ. PiSZ individuals probably have some increased
risk of lung or liver disease. As for persons who are Pi MZ, Pi SZ
M M M Z
individuals should be reassured regarding their potential risk for M Z Z Z
developing lung or liver disease, and counseled about the risk of
genetic transmission of the deficient allele. PiSZ individuals should CHILDREN
also avoid tobacco smoking.
Normal (MM) Does not have the disorder and does
not carry any altered AAT genes.
Carrier (MZ) Mild to moderate AAT Deficiency - may
Genetic transmission of AAT Deficiency follows simple Mendelian
develop disease symptoms and does
principles. Individuals with AAT Deficiency have two deficient carry an altered AAT gene.
alleles for the protein (e.g. Z and/or null allele). Thus, the Carrier (MS) It is unclear whether there is a risk for
deficiency is inherited similar to an autosomal recessive condition. developing disease symptoms but
Brothers and sisters of deficient individuals have a significant does carry an altered AAT gene
(though most studies do not indicate
chance of also having the condition. Children of deficient an increase risk for disease).
individuals are usually heterozygous (a “carrier”) for the deficiency AAT Deficiency (ZZ) (SZ) Moderate to severe deficiency - could
(assuming the patient’s spouse is a Pi M). Among U.S. develop disease and does carry two
Caucasians, approximately 3% are carriers. These people often altered AAT genes.
have reduced levels of the protein, but have minimal excess risk AAT Deficiency (SS) It is unclear whether there is a risk for
of lung or liver disease. Phenotyping is necessary to reliably developing disease symptoms but
does carry two altered AAT genes
detect carriers, since AAT levels of normal individuals and carriers (though most studies do not indicate
overlap to some extent. an increase risk for disease).
Family History: • Diffusion capacity
A positive family history of AAT Deficiency is the greatest risk • Arterial blood gases
factor for AAT Deficiency. The implications for finding ALL family • Liver function test, including:
members who may be carriers are of great importance.
Identification of Patients: • ALT
You should test adult patients with the following problems, as • Alkaline Phosphatase
recommended by the World Health Organization (WHO):
• Total and Direct bilirubin
• Albumin, clotting studies (PT, INR, PTT)
• Liver ultrasound examination
• Family history of AAT Deficiency
• Alpha Fetoprotein
• Chronic liver disease
Other conditions not specifically recommended by WHO, but Testing:
possibly indicating increased risk for AAT Deficiency include: In general, testing for AAT consists of an immunoassay for AAT
levels followed by phenotyping. Phenotyping is performed:
(1) If the level AAT is abnormal, and/or,
(2) If there is a known family history of AAT Deficiency, and/or,
• Unexplained vasculitis, particularly of Wegener’s
granulomatosis type (3) If there is otherwise unexplained liver disease
• Hepatocellular carcinoma
Individuals found with a serum level of 11µM or less or a
• Any evidence of unexplained liver disease
deficient phenotype are considered to have AAT Deficiency.
It is important to understand that if these conditions are seen in
Newer testing methods utilize a finger stick test that measures
non-smokers of any age, or if COPD occurs at an early age (age
both AAT levels and genotype (type of AAT gene in DNA).
30 to 55) in smokers, the likelihood of AAT Deficiency is increased.
Testing At-Risk Patients: Phenotype & AAT Deficiency Risk:
After confirming the AAT Deficiency status of your patient, you may
Phenotype Serum AAT Range (µM)*
want to consider the following tests for collecting baseline data:
Pi M 20-48
Baseline Examination Pi MZ (heterozygotes) 12-35
• Physical Exam Pi S 15-33
• Postero-Anterior (PA) and Lateral Chest X-Ray or a high Pi SZ (heterozygotes) 8-19
resolution CT of the lungs
Pi Z 2.5-7.0
• Pulmonary function test, including:
• Spirometry curves (before and after inhaled bronchodilator)
* µM result can be derived from mg/dl by multiplying mg by .1923.
• Lung volumes
There are several forms of treatment listed in this brochure for lung function impairment is seen in current or former smokers.
the confirmed AAT deficient patient, including these four major Smoking attracts white blood cells to the lungs in large numbers
areas: Behavioral & Lifestyle Modification, Drug Therapy for and speeds the development of lung disease. The lungs in AAT
Lung Problems, Specialized Therapy for AAT Deficiency, and deficient patients do not have the normal defenses against the
Surgical Options. white blood cells and neutrophil elastase.
The Alpha-1 Foundation is an important resource for the
2. Avoiding Environmental Pollution
physician with an AAT deficient patient. The Foundation:
Although formal studies are lacking, it is probably advisable for
• Provides a list of over 50 Clinical Resource Centers (CRC’s)
Alphas (persons with AAT Deficiency) to avoid occupational and
and physicians who specialize in the care of AAT deficient
environmental pollutants that can be inhaled (including pollen,
patients. It may be of value to have your patient seen once a
dust, areas with high levels of air pollution, and secondhand
year at a Center to monitor their AAT Deficiency and
tobacco smoke). These substances can cause further irritation
coordinate their care with you. Many CRC’s have available
of the lungs and worsen the current condition of the patients
specialized tests that can serve as a valuable tool in detecting
disease and monitoring its progression.
Avoid both indoor and outdoor air pollution such as particulates
• Provides regular updates on AAT Deficiency research activities
smaller than 10 µm (found in higher industrialized urban regions)
and announcements on newly approved treatment products
and exposure to aerosolized sprays. It is also important to
realize that your patient(s) may encounter pollutants and
• Provides access to its Medical Director for consult, infections at both home and at work, thus recommend
information, and referral. precautions in both places.
• Gives the patient an opportunity to get involved in their
■ In the Workplace
personal treatment, by talking and meeting other Alphas
through computer and telephone access. Contact (and refer Patients should avoid exposure to inorganic or organic dust,
your patients to) the resources listed at the end of this guide (i.e., coal, hay, etc.) or irritating gasses (i.e. chlorine,
for more information and for support and advice for your isocyanates, etc.). Your patients should seek the healthiest
patients in making these important lifestyle changes. possible work environment, and demand clean indoor air, with
proper ventilation and filtration systems and avoid secondhand
Behavioral & Lifestyle Modification tobacco smoke whenever possible. Wear protective clothing, i.e.,
Individuals with AAT Deficiency should NEVER smoke. Evidence gloves, etc., when handling any type of chemical compounds
shows that smoking tobacco products significantly increases the since they may be absorbed through the skin and could further
risk and severity of emphysema in AAT deficient individuals and damage an already compromised liver. Read labels carefully
may decrease their life span by ten years or more. Exercise and and be aware of potential dangers from these agents.
nutritional plans also contribute to maintaining a healthier body,
■ In the Home
which places less stress on the lungs. These three issues are
explored in further detail below: Advise your patients to avoid certain household chemicals, such as:
• Respiratory irritants
1. Smoking Cessation
• Chlorine and ammonia (found in common household cleaning
This is the first priority in managing patients with AAT Deficiency.
Lifelong non-smokers will have a good chance of avoiding
serious lung disease, even with AAT Deficiency. Current smokers • Pesticides
should stop smoking upon diagnosis, since the most severe
Since bacterial and viral infections are harmful to the lungs, patients with liver failure, good nutritional advice is recommended.
recommend that your patients try to avoid contact with sick or In the AAT deficient patient who exhibits signs of liver complications,
infectious people. Handwashing with an antibacterial soap is the fat absorption may be altered; therefore the physician may
single most effective way to avoid both contracting and recommend supplementing the diet with Vitamins A, D, E, and
spreading infectious diseases. K. A special formula is often recommended for an infant
experiencing feeding difficulties, showing poor growth and a
3. Development of an Exercise Program
failing to thrive.
Although formal studies are lacking, routine exercise can
Recommend to your patients that they should establish or
improve mental outlook, stamina and physical well being.
maintain good eating habits. If your patient has lung and/or liver
Exercise is essential to all Alphas.
problems, it may help to work closely with a nutritionist or
• Supervised aerobic and strength exercises should begin as registered dietician, who will be able to set up an appropriate,
soon as possible after diagnosis. individualized nutritional plan.
• Walking programs (particularly in climate controlled local
5. Reducing Stressors
indoor shopping malls), strolling, swimming, and/or biking can
facilitate exercise, which may be beneficial in improving lung Persons with AAT Deficiency (Alphas) report benefits with stress
function and endurance. reduction techniques.
• It is important for all Alphas to have personally tailored There are many relaxation techniques that help in reducing
exercise programs carefully monitored by you and/or an stress. Here are a few:
exercise specialist. Patients should start exercising slowly and • Breathing exercises
increase levels of exercise over time, as the patient’s tolerance • Muscle relaxation
for exercise increases. Some physicians recommend the use
of a portable oximeter during exercise.
A Pulmonary Rehabilitation Exercise Program (PREP) is highly
recommended for Alphas. PREP can help an individual with • Hypnotherapy
pulmonary disease through exercise, breathing retraining, • Positive thinking
education, smoking cessation, and nutrition counseling. You
• Improving sleep patterns
should recommend and discuss a program tailored to your
patient’s specific needs. • Yoga
4. Alcohol Consumption
Information on these relaxation techniques is available at local
Alcoholic beverages can damage the liver even in normal
libraries and bookstores or through the resources listed at the
people. Many authorities recommend low, infrequent or no
end of this guide.
alcohol consumption for ZZ patients. Patients with any indications
of AAT-related liver damage should avoid alcohol completely.
Drug Therapy for Lung Problems
5. Development of a Nutrition Program This is among the most important type of medical therapy for the
Although there is a lack of formal research regarding the effects newly diagnosed individual with AAT Deficiency.
of specific nutritional recommendations, proper eating habits 1. Vaccinations (influenza/pneumonia)
may help to preserve lung and liver function.
It is important for your patient to have a yearly influenza vaccine
It is important for your patient to maintain an ideal body weight, and a Pneumovax® shot every five to six years. Since his/her
whether he/she has lung/liver disease or not. Since scientific lungs are vulnerable to pollutants and infections, the use of
research indicates that people with lung disorders need to these prophylactic vaccinations is of the utmost importance.
consume more calories than “lung-healthy” people, this affects Furthermore, your patient may find this the easiest and most
the manner in which your patient should approach nutrition. convenient type of therapy available. Effective vaccines are
Supportive nutritional needs in those patients exhibiting liver available for hepatitis A and B. These are especially important in
complications due to AAT Deficiency are highly individualized. patients with established liver disease.
Since sodium and protein intake may become a concern in
Recommendations: • Fever
• Annual influenza vaccine • No appetite/refusal to eat or drink
• Administration or confirmation of Pneumovax vaccine • Itching or increased itching
(consider every five to six years) • Peripheral edema
• Hepatitis A vaccine • Change in or the appearance of jaundice
• Hepatitis B vaccine It is very important to inform the individual to carefully read the
2. Aggressive Treatment of Lung Infections labels on over-the-counter medications and to be certain to
inform the healthcare provider if alternative medicine (i.e., Milk
Prompt and aggressive treatment of infections is recommended
Thistle) or vitamin supplements are being taken.
due to the increased neutrophil elastase burden during infection.
It is important for you to recommend to your patients that they 4. Bronchodilators
notify you immediately when they suspect a lung infection. Here Bronchodilators may be useful in relieving the symptoms of AAT
is a list of common symptoms they should be advised about: Deficiency. Depending on the specific medical history and
• Fever present condition of the patient, you may advise the use of
• Increased shortness of breath bronchodilators.
• Increased coughing (may not be productive) 5. Corticosteroids
• Chills with fever Inhaled corticosteroids can be useful as a preventative
treatment for AAT Deficiency and oral corticosteroids may be
• Changes in color of phlegm
helpful during exacerbations.
Because the lungs attract more leukocytes when an infection is
present, and the leukocytes release neutrophil elastase, it is 6. Supplemental Oxygen
important to control lung inflammation. Antibiotics may help to For people who need supplemental oxygen, it has been shown
speed recovery. to be lifesaving. Oxygen can be important for individuals with
Another piece of preventive advice for the patient should be: low blood oxygen levels, during active infections and/or with
progressive destruction of the lung tissue. Supplemental oxygen
• Avoid people who are sick (infected individuals).
may be needed during exercise and/or sleep.
• Avoid children less than five years of age (they are often
Supplemental oxygen is also recommended during exercise.
infectious or exposed to infections).
For some Alphas, it is especially important when traveling by air,
3. Aggressive Evaluation of Liver Complications because cabin pressure changes with altitude.
It is important for parents, caregivers or significant others to be 7. Specialized Therapy for AAT Deficiency
aware and advised of any indication of complications related to
There is a specific treatment for AAT Deficiency called
augmentation therapy. Augmentation therapy increases the lung
Here is a list of common symptoms that may require therapy: levels of AAT. Augmentation therapy is not a cure; it will not
• Increased abdominal swelling or edema of the extremities reverse the lung damage that has occurred nor treat or prevent
AAT Deficiency-related liver problems. Contact the resources
• Coughing up or vomiting bright red blood
listed at the end of this guide for the latest standard of care
• Blood in toilet or diaper related to the use of augmentation therapy.
• Blackish, purplish or dark colored stools
• Confusion, crankiness, unusual crying, disorientation, lethargy
Augmentation therapy, a derivative of human plasma, is the only
• Little or no urine currently available treatment for AAT Deficiency. It is used to
• Dark (tea or cola-colored) urine increase the concentration of AAT in the blood and lungs.
However, long-term controlled clinical trials have not been
• Lack of energy, easily fatigued
done to show that augmentation therapy alters the course • Lung Volume Reduction Surgery (LVRS)
of lung disease. • Organ Transplantation of Lung or Liver:
Clinical Criteria for Use Lung/liver transplantation is becoming a viable option for some
patients. As experience with new surgical techniques (particularly
• Currently, augmentation therapy can only be prescribed for
single lung transplantation) increase, lung transplantation may
patients with AAT Deficiency-related emphysema. This is not a
become more attractive to AAT deficient patients with end-stage
treatment option for AAT Deficiency related liver disease.
lung disease. Utilization of this therapy is only for patients with
Augmentation therapy cannot be recommended for individuals
end-stage lung or liver disease. The option of living-related liver
with normal lung function. It should be reserved for those AAT
transplantation is available at some transplant facilities.
Deficiency patients with phenotypes Pi Z, Pi Z/null, Pi null null,
and/or patients who have AAT serum levels < 11 µM. It should Large volume paracentesis (LVP) may become necessary in end
not be given to those individuals who do not have AAT stage liver disease when diuretic therapy is inadequate in the
Deficiency or to individuals with mildly deficient phenotypes. treatment of ascites. Portal vein decompression utilizing surgical
shunts has long been known to be effective means of relieving
• Augmentation therapy can be administered in the physician’s
intractactable cirrhotic ascites and in the treatment of portal
office or in a facility where intravenous infusions are routinely
hypertension when there is evidence of esophageal varices.
given for other indications. Home administration is also an
The portocaval shunt surgical procedure, either side-to-side or
option; several companies offer home infusion services.
end-to-side is often used if more conservative measures utilized
• Some patients infuse themselves or have a spouse, relative, or in controlling bleeding, such as sclerotherapy or band ligation,
friend perform the infusion. are ineffective. The TIPS (transjugular intrahepatic portosystemic
shunt) procedure has also been effective in controlling bleeding
Safety of Augmentation Therapy
from esophageal or gastric varices, as well as controlling
• Augmentation therapy is prepared from pooled human plasma
cirrhotic ascites. Surgical treatment options are highly
that has been screened for Hepatitis A, B and C and tested for
individualized to each patient, as is the decision as to the timing
human immunodeficiency virus. As an additional precaution
of liver transplantation.
against transmission of infectious agents, the product is heat-
treated during the manufacturing process. For further As with all surgery, outcomes depend on a number of issues
protection, administration of the hepatitis B vaccine is specific to each person. There are no guarantees for the extent
recommended prior to therapy. to which there will be improvement of medical condition. Please
consult with your patient about these options, if appropriate.
Known Side Effects • With AAT Deficiency, one of the last options is organ
• There are relatively few side effects reported: headaches, transplantation. Utilization of this therapy is for those
myaligias, arthaligias, and low back pain are most frequent patients who:
complaints by patients on therapy, but require no treatment or • Do not respond to more conservative therapy.
occasional analgesic use. For patients with severe COPD or
• Have extensive damage of the lungs or liver.
heart failure, worsening of shortness of breath may occur.
• It is important to be aware that patients who have both AAT
Deficiency and IgA deficiency can develop acute anaphylaxis
when given augmentation therapy. Therefore, these patients
should NOT receive augmentation therapy.
As the patient’s physician, you determine the rationale for use
There are two major types of surgery for those patients with
Q: Should I encourage my patient to discuss AAT
Once your patient is diagnosed as having AAT Deficiency, Deficiency testing with other family members?
he/she may feel overwhelmed and have many questions.
A: Yes. It is advisable to encourage your patient to inform
To provide a more comprehensive approach to talking
his or her family members about the genetic aspects of
with your patient about the ramifications of an AAT
AAT Deficiency and encourage them to seek genetic
Deficiency diagnosis beyond a purely medical discussion,
counseling. Those who have symptoms, as noted in the
it may be helpful to review the following material.
WHO recommendations, should be encouraged to be
tested. Other family members should be urged to
The purpose of this section is to give you several scenarios that educate themselves about the disorder and be vigilant
may arise when dealing with an AAT deficient patient. Each for the development of symptoms.
scenario is merely a starting point. Contacting the resources at
the end of this guide will provide you and your patient(s) with
more in-depth support and strategies for addressing each If both parents are carriers, each child has a chance of
situation, from the perspective of a person living with AAT inheriting AAT Deficiency, a chance of being a carrier of AAT
Deficiency. These topics include: Deficiency, or a chance of having both normal genes.
1. Psychosocial/Family support 2. Health Insurance/Life Insurance
2. Health insurance Insurance is a major issue for patients diagnosed with AAT
3. Employment Deficiency. Here are some questions that patients may ask:
4. Reimbursement/Insurance claims Q: Will the AAT Deficiency diagnosis affect my health
5. Confidentiality insurance?
1. Psychosocial/Family Support A: It may. The extent to which it specifically affects health
The most useful steps the patient can take to reach out for insurance (continuing and acquiring new policies)
support is to contact one of the resources listed at the end of depends upon their current insurance coverage status.
this guide. These organizations exist to help people with AAT If your patient is currently insured:
Deficiency all over the country. The patient can speak and even
Instruct your patients to educate him/herself regarding:
meet other people with AAT Deficiency who can provide support
and additional information. • Specific insurance policy and benefits regarding coverage
Remember to reassure your patient that you are here to assist
them along the way, and will answer any questions that will • Lifetime maximum benefits, if any.
console him/her. Getting actively involved with the overall • The laws in your patient’s state regarding mandatory coverage.
treatment of the patient, which will extend into other aspects of
the patient’s life, is of utmost importance. If your patient is currently uninsured:
AAT Deficiency is considered a pre-existing condition, and
Q: What do I tell my patients about informing their family
future insurance companies may not be obligated to cover costs
for this specific condition for some period of time. You may
A: We recommend that, after discussion with you about direct your patient to seek professional advice and recommend
the discriminatory issues surrounding AAT Deficiency that they familiarize themselves with the insurance regulations in
that they suggest to blood relatives to seek testing, their state of residence. In general, your patients are obligated
because of the genetic nature of the disorder. to inform an insurance company of any pre-existing condition
when they apply for coverage.
3. Employment Establishing and maintaining confidentiality in the doctor-patient
relationship is always the best way to have the trust of your
Q: Can your patient continue to work? patients. Breaching this trust can produce devastating results.
A: The answer to this question usually depends on two You should discuss the following confidentiality issues with your
• The present state of your patient’s health
Q: Who will know the patient’s AAT Deficiency diagnosis?
• The possibility of unwanted airborne exposures (i.e., dust,
fumes or other environmental hazard) at work A: The results of the test will be included in a patient’s
medical record. Although generally treated as confidential,
It is good for Alpha patients to work! Please discuss with your
inform the patient that insurance companies, healthcare
patient his/her health status and assess the possibility of
facilities and other professionals may access this
occupational exposure to dust and fumes. If your patient is in
acceptable health and has no occupational exposure to dust
and fumes, then your patient can continue to work. Otherwise, Q: To whom should (or must) the patient disclose the AAT
you may suggest the possibility of him/her changing jobs to Deficiency diagnosis?
reduce these exposures.
A: Patients must make their own decisions about
Please note that continuation of health insurance coverage, if
discussing this information. However, it is highly
your patient changes jobs after diagnosis, may vary from state
recommended that the patient tells his/her blood
to state. The issue of disclosure of this diagnosis may also affect
relatives about the risk and urge them to seek testing.
the benefit status of future coverage.
Patients should inform future healthcare providers, and
Q: What role does disability insurance have? may have to inform insurance companies, if there is a
change in policy.
A: If your patient’s physical condition does not allow
him/her to work, it is important to discuss the availability
of disability insurance payments with your patient.
Disability insurance will help pay for your patient’s medical
care; however, it may severely limit your patient’s ability to
work in the future.
Finding out about an AAT Deficiency diagnosis
4. Reimbursement/Insurance Claims can be an overwhelming and potentially upsetting
Each individual diagnosed with AAT Deficiency should contact experience. It is important for the patient to share
his/her insurance company concerning insurance coverage and this information with his/her family, and to seek
reimbursement issues. If augmentation therapy is recommended, professional psychological counseling, if necessary.
a service of the Alpha -1 Foundation is to assist in the preparation Each newly diagnosed patient should be
of supporting documentation requested from the patients by the encouraged to seek more information and
insurance company regarding the use of augmentation therapy support. It is recommended that your patient get
and/or other options (see Treatments). more information as soon as possible after
Most health care insurance companies will cover the drug and diagnosis by talking with persons living with AAT
administration costs of the augmentation therapy. However, Deficiency and to identify support for himself/
benefits may vary depending upon when and where the therapy herself and family members. (See the end of this
is administered (i.e., in your office, a hospital, a separate guide for contact organizations.)
infusion clinic, or at home).
The objectives of these materials are to increase physician these issues should be carefully considered prior to being tested.
awareness of AAT Deficiency and to promote screening (of “Your choice to be tested is totally voluntary. You are free to
patients at risk). It is important for you to be able to explain the refuse to be tested at any time.”
disorder in a clear and concise manner and encourage testing
Again, as your doctor, I would be happy to answer any
of your patients at risk. Through a simple blood test, you can
questions concerning AAT Deficiency, and your possible risk.
identify affected patients and receive results within two weeks.
At this point, provide the patient with the brochure, “What Is
Following are scenarios that were developed to assist you in
Alpha-1 Antitrypsin Deficiency? Should I Be Tested?”
encouraging screening, giving test results and explaining the
various aspects of an AAT Deficiency diagnosis. Giving Test Results
Promoting Screening Alternative A
Setting: In-Office Visit Setting: Office Visit
Objective: Request Blood Sample Objective: Explain a Negative Test Result
“As one of my patients with the diagnoses of (emphysema, (Pi M) for AAT Deficiency
COPD, bronchiectasis, liver disease, etc.) I am advising you to “After reviewing the results of the blood test we performed at
consider being tested for the genetic disorder AAT Deficiency. your last visit to determine if you had the inherited genetic
disorder AAT Deficiency, I am pleased to inform you that the
AAT Deficiency is believed to affect as many as 100,000 people
results were negative. This means that you have enough
in the US alone, making it one of the most common genetic
alpha1-antitrypsin (AAT) in your blood, and indicates that you
disorders in this country. Since AAT Deficiency was only recently
do not have the disorder.”
discovered, there is much to learn about its frequency, severity,
treatment and prevention. I am advising you to consider this test Despite the negative result, you should still advise patients that
because this information will be important to help me take better it is important to avoid all tobacco smoke, whether it is from
care of you as a patient. By taking the test, you will learn directly smoking tobacco products or situations where it is
whether or not you have the genetic disorder called AAT inhaled secondhand.
Deficiency. Early detection of AAT Deficiency is very important Alternative B
because there are medical interventions I can prescribe that
may help to prevent or prolong the time before the damage to Setting: Office Visit
your lungs occurs. I can discuss these interventions with you. Objective: Explain a Carrier Test Result
The only way to be tested for AAT Deficiency is to have a blood (PI MZ or Pi MS) for AAT Deficiency
test. This test will only take a few minutes and uses a finger “After reviewing the results of the blood test we performed at
stick. The results generally require a two-week period of time to your last visit to determine if you had the inherited genetic disorder
receive. Once the test results are back, I will contact you by AAT Deficiency, I must inform you that the results were positive
telephone to come in for a follow-up visit to discuss your results. for a special state of the disorder known as the carrier state.”
There may be some mild physical discomfort and risk of an “Heterozygotes (carriers) have one normal gene and one gene for
infection from obtaining the finger stick blood sample for the the disorder. This combination of genes does NOT typically cause
blood test. You may experience slight discomfort at the needle health problems. Currently, the risk of lung or liver problems for
site and there is a risk of a bruise. yourself appears to be low.” There have been published research
There are ways your life could be affected by learning information that findings that have indicated that there may be a higher risk for
may be discovered by genetic testing. There may be additional risks, developing chronic liver disease in the adult PI MZ population
including emotional distress, which I cannot predict at this time. All of either alone or in combination with other liver diseases.
“However, it is recommended that you should inform your blood B. Review information in the manual, “A Guide for the
relatives of the test result because of the genetic nature of the Recently Diagnosed Patient”
disorder. Since AAT Deficiency is passed genetically from parents
C. Schedule the next patient visit; and
to child, it is possible that your blood relatives could be
heterozygotes (carriers) such as yourself, or have AAT Deficiency. D. Complete the Treatment Checklist
Another important aspect of this test result is that you can pass on E. Provide information and questionnaires for each family
the gene to your children.” member from the Alpha-1 Research Registry.
Example: Alternative D
If both parents are carriers, each child has a chance of
inheriting AAT Deficiency, a chance of being a carrier of AAT Setting: Office Visit
Deficiency, and a chance of having both normal genes. Objective: Explain a Positive Test Result
Most importantly, you should advise patients that it is important Pediatric Patient - Liver Disease
to avoid all tobacco smoke, whether it is from directly smoking “After reviewing the results of the blood test we performed at your last
tobacco products or situations where it is inhaled secondhand. visit, to determine if your child had the inherited genetic disorder AAT
At this point, you can provide the patient with the brochure Deficiency, I must inform you that the results were positive for the
“A Guide for the Recently Diagnosed Carrier” and the Alpha-1 disorder. The amount of alpha1-antitrypsin in your child’s blood is low,
Research Registry questionnaires for family members. and the alpha1-antitrypsin (AAT) in your child’s blood is slightly
different from the normal type. However, your child’s liver disease is
Alternative C not due to this low level of AAT in the blood stream. Research studies
indicate that these liver complications are the result of the misfolded
Setting: Office Visit
protein not being secreted properly into the blood stream. This
Objective: Explain a Positive Test Result backup of AAT in the individual liver cells causes damage to the liver.
(Pi Z) for AAT Deficiency and its consequences
At this time, there is no specific treatment for liver disease
Adult Patient - Pulmonary Disease associated with AAT Deficiency. Clinical care is primarily
“After reviewing the results of the blood test we performed at supportive management for any liver dysfunction and prevention
your last visit, to determine if you had the inherited genetic of complications. Each child is an individual and treatment is
disorder AAT Deficiency, I must inform you that the results were highly individualized. Liver transplantation may be required. It is
positive for the disorder. The amount of alpha1-antitrypsin in your difficult to say if your child will definitely need a liver transplant.
blood is low, and the alpha1-antitrypsin in your blood is slightly The majority of these children diagnosed with AAT Deficiency
different from the normal type. This test result explains some of have a low rate of disease progression and lead a relatively
the health problems that you are experiencing (or have normal life for extended periods of time.
experienced) including [symptoms specific to this patient, i.e.,
coughing, wheezing, shortness of breath]. A. Explain
• The course of Alpha-1 Antitrypsin Deficiency
I know that this can be upsetting news, due to the impact that
having this disorder may have on your health. However, with • The progression of Alpha-1 Antitrypsin Deficiency
behavioral and lifestyle modifications such as not smoking, exercise, • Consequences, including the genetic risk to the patient’s family
nutrition, drug therapy, medical treatments, specialized therapy for
B. Review information in the manual, “A Guide for the
AAT Deficiency, and preventive measures, Alpha patients can and
do lead full lives and enjoy relatively stable lung function. Recently Diagnosed Patient”
Before we go into the explanation of what this means and the C. Schedule the next patient visit; and
questions you may have, let me review the information we have F. Complete the Treatment Checklist
about Alpha1 at the present.” G. Provide information and questionnaires for each family
A. Explain member from the Alpha-1 Research Registry.
• The course of Alpha-1 Antitrypsin Deficiency
At this point, make sure that you note your counseling
• The progression of Alpha-1 Antitrypsin Deficiency discussion in your patient’s medical record.
• Consequences, including the genetic risk to the patient’s family
for AAT Deficiency
Many patients will experience emotional upset and anxiety due Assess smoking status and give a strong message to quit
to their diagnosis. It may be necessary to schedule an additional if patients smoke any form of tobacco, including cigars
visit in order to complete discussion about recommended and cigarettes
medical treatment and behavioral changes.
Discuss risk of occupational and environmental exposures,
1. Initial Visit(s) including second-hand tobacco smoke and dusts
Discuss baseline testing (with subsequent follow-up) Avoid being around exposed individuals who are ill with the
Discuss requirement for lung function tests (FEV1, etc.) Flu or a cold, etc.
Discuss need for baseline liver evaluation or referral to a Discuss alcoholic beverage consumption
GI/Liver specialist (Pediatric or Adult) Discuss developing an exercise program
Discuss need for baseline lung evaluation or referral to a Discuss developing a nutrition program
pulmonologist (Pediatric or Adult) Discuss reducing stressors
Discuss the use of drug therapy for lung problems Discuss referring patient to a counselor (if necessary)
Use of bronchodilators Contact and refer patients to the resources listed at the end
Use of corticosteroids of this guide
Aggressive treatment of lung infections 2. Subsequent Visit(s)
Discuss aggressive treatment of liver complication symptoms. Discuss requirement of follow-up visits
Discuss need for vaccinations Augmentation therapy (specialized therapy
Influenza (annual) for AAT Deficiency)
Pneumovax® (every six years) Discuss use of supplemental oxygen (if necessary)
Hepatitis A Discuss surgery options (if appropriate)
Hepatitis B Discuss referring patient to a counselor (if necessary)
Alpha-1 Antitrypsin Deficiency
The Alpha-1 Research Program at the University of Florida in • The Alpha-1 Translational Research Laboratory is devoted to
Gainesville was established by the Alpha-1 Foundation and is characterizing the molecular mechanisms responsible for the
devoted to the study of lung and liver disease associated with development of liver and lung, disease in AAT Deficiency and
Alpha-1 Antitryspin Deficiency (AAT Deficiency or Alpha-1). to the development of new treatments.
The resources and services offered by the Program are an • The Alpha-1 Gene Therapy program is focused on the
important access point for the national and international medical development of safer and more efficient vehicles for the delivery
and scientific communities. These resources include: of therapeutic genes to the liver, lung, and other tissues.
• The Alpha-1 DNA and Tissue Bank serves the international • The Alpha-1 Florida Detection Program is a state sponsored,
scientific community with the largest single-disease collection of statewide, targeted population screening for AAT
DNA and tissue samples for research studies in the United States. Deficiency. The Alpha-1 Florida Detection Program targets
• The Bronchoscopy Research Procedure Unit and the Lung Cell Florida residents with Chronic Obstructive Pulmonary
Biology Laboratory enable clinical studies on the fundamental Disease (COPD) and liver disease. The Program is
process associated with lung injury in individuals with AAT dedicated to raising awareness among Florida medical
Deficiency and determine the efficacy of new therapies. professionals, the media, and the public about AAT
Deficiency. Through this Program, diagnostic testing for AAT
• The Alpha-1 Genetics Laboratory is an International Reference
Deficiency is offered free of charge, and appropriate
Laboratory for AAT levels, phenotype, and genotype analysis.
referrals for education and clinical care are made.
Testing is provided free of charge to patients throughout the
world and includes: For a free test kit and/or for more information on the programs
and services of the University of Florida Alpha-1 Research
• Alpha-1 Antitrypsin Genotyping, Phenotyping and blood
• Follow-up and/or referral for specialized care University of Florida College of Medicine
Toll Free Telephone: 1-866-284-2708
• Genetic Counseling Referral
• Alpha-1 Specific Patient Educational Resources
Organizations & Resources
■ The Alpha-1 Research Registry... is a confidential database
There are a number of organizations, which help and of AAT deficient individuals and Alpha-1 Carriers that
support people with AAT Deficiency. Each of these provides the population base eligible for clinical trials and
organizations works with the AAT deficient individual research studies. The Registry is administrated by the
in different ways. Medical University of South Carolina.
■ Alpha-1 DNA & Tissue Bank... serves the international
Alpha-1 Foundation scientific community with the largest single disease collection
Toll Free: 877-2-CURE-A1 (228-7321) of Alpha-1 DNA and tissue samples for research studies.
Web Site: www.alphaone.org It is located at the University of Florida College of Medicine.
The Alpha-1 Foundation is a not-for-profit organization founded ■ The Alpha-1 Research Network... provides support for and
by individuals diagnosed with Alpha-1 Antitrypsin (AAT) consultation with an international network of scientists who
Deficiency. Its mission is to provide the leadership and volunteer their time and expertise through service Boards,
resources that will result in increased research, improved Committees and Working Groups. The network is also
health, worldwide detection and a cure for Alpha-1. This comprised of over 50 Clinical Resource Centers, including
mission is achieved through the following programs and activities: pulmonary and liver centers where AAT deficient individuals
■ An Alpha-1 Research Grants and Award Program... has are referred for expert care and have the opportunity to
funded to date over $7 million in a broad range of research participate in clinical trials and research studies.
grants and awards.
■ Scientific Meetings, Conferences, Workshops, Working Alpha-1 Association
Groups and Symposia... focus on specialized topics to
Toll Free: 800-521-3025
advance knowledge of AAT Deficiency and address critical
issues in the areas of improved treatments, education, Toll Free: 800-4ALPHA1 (425-7421)
detection and ethical issues. Web Site: www.alpha1.org
■ An Alpha-1 Detection Program... promotes worldwide The Alpha-1 Association is a not-for-profit, membership
awareness and the identification of AAT deficient individuals organization founded in 1991. The community of people who
in population groups at high risk for AAT Deficiency such as are affected by Alpha-1 governs this international organization.
adults with Chronic Obstructive Pulmonary Disease (COPD), Its mission is “to identify those affected by Alpha-1 Antitrypsin
chronic asthma and/or chronic liver disease. Deficiency and to improve the quality of their lives through
support, education, advocacy, and research.” That mission
■ Public Policy and Advocacy... Government relations activities
is fulfilled through an international network of support groups;
in Washington respond to the challenge of increasing
a Peer Guide program to help newly diagnosed individuals,
research funding, addressing product shortages, ensuring
and an array of educational materials. The Alpha-1 Association
blood safety, developing new therapies and advocating for
advocates for the community on a host of issues including
access to care, which includes insurance reimbursement and
genetic privacy and discrimination, insurance issues, and
product safety and availability. The Association also encourages
■ University of Florida at Gainesville, Alpha-1 Research research and supports the programs of the Alpha-1 Foundation.
Program… The University of Florida College of Medicine
Alpha-1 Research Program was established by the
Foundation as a resource to the medical and scientific American Liver Foundation
community. Toll Free: 800-GO-LIVER (465-4837)
AlphaNet Web Site: www.liverfoundation.org
The American Liver Foundation is a national, voluntary not-for-
Toll Free: 800-577-ANET (577-2638)
profit organization dedicated to the prevention, treatment, and
Web Site: www.alphanet.org cure of hepatitis and other liver diseases through research,
AlphaNet, a not-for-profit disease management company, education and advocacy.
currently employs more than 20 Alphas. AlphaNet provides a
wide range of support services to patients, administers clinical American Lung Association
trials involving Alpha-1 therapies, and has developed a Toll Free: 800-LUNG-USA (586-4872)
comprehensive disease management program to enhance the Web Site: www.lungusa.org
quality of life for those affected by Alpha-1. Since its inception in The American Lung Association (ALA) is a nationwide health
1995, AlphaNet has contributed over $10 million to support organization. Since 1904, the American Lung Association has
Alpha-1 research and community programs. been fighting lung disease through education, community
service, advocacy and research, seeking better treatments and
cures. The ALA can also help you find information on smoking
cessation programs that are available.
Funding for this brochure is provided by an unrestricted educational grant from AlphaNet.